U.S. Pat. No. 6,676,963 to Lanza, et al., incorporated herein by reference, describes drug delivery in general using targeted “oil-in-water” emulsions, typically emulsions of nanoparticulate fluorocarbon cores coated with lipid/surfactant layers, wherein the lipid/surfactant layer contains a drug to be delivered as well as a targeting agent. As explained in this patent, the prolonged association of the targeted emulsion particles with the surface of a target cell or tissue is distinct from a transient interaction of a non-targeted particle. By binding the particle to the cell surface, the continued circulation of the nanoparticle through the body is halted and the affixed particle is able to interact with the target cell membrane (which is a lipid bilayer) over an extended period of time. This permits effective delivery of the drug contained in the lipid/surfactant layer.
None of the drugs contemplated by Lanza, et al., are membrane-integrating peptides that may undergo endocytosis or that may form pores in the lipid bilayer cellular membrane which can result in cell death due, for example, to non-specific control of substances that enter and exit the cell. These peptides present particular problems and are generally not practical as, for example, antitumor agents, due to their nonspecificity and frequently their overall cytotoxicity in vivo.
Various alternative nanoparticulate compositions containing hydrophobic cores and lipid/surfactant coating are described in U.S. Pat. Nos. 7,255,875 and 7,186,399, both incorporated herein by reference. These patents also refer to earlier compositions used as contrast agents that lack targeting agents.
The problems associated with administering membrane-integrating peptides have been solved by the present invention which resides in the discovery that by associating the membrane-integrating peptides with a lipid/surfactant layer surrounding a hydrophobic core, and optionally targeting the peptide-containing nanoparticle to a tissue for example one whose demise is desired, delivery to this target cell or tissue can be effected so that the peptide can inhibit the growth of the target cells or, indeed, effect cell death while the surrounding tissues and non-target cells are unaffected. The peptide can also facilitate delivery of other therapeutic or diagnostic agents. In addition, the peptide, by virtue of its protected status, is delivered without prior degradation.